Phototherapeutic Nanodrugs Based On Polyethylenimines

In recent years,photodynamic therapy has been widely used in clinical trials as a non-invasive or minimally invasive therapy.However,most photosensitizers(PSs)have the disadvantages of poor water-solubility,severe self-quenching,and potential toxicity.To address the above issues,in this thesis,we prepare a biocompatible cholesterol-polyethyleneimine(Chol-PEI)cationic polymer conjugated with a photosensitizer,which can be self-assembled into nanoparticles(NPs)for use as a nanoparticulate drug delivery system.The Chol can be effectively anchored to the cell membrane and enter the cell by lipid raft-dependent endocytic pathway;PEI is a water-soluble cationic polyelectrolyte which can effectively bind to or enter negatively charged cells or tissues.The photosensitizer linked to the polymer not only has improved water-solubility,but also has enhanced cellular uptake.This thesis includes the following two chapters to evaluate the potential of the photosensitizerloaded Chol-PEI for the antibacterial and anticancer applications.1.Ce6-loaded Chol-PEI for antibacterial photodynamic therapyThe Chol-PEI-Ce6 could self-assemble into nearly spherical NPs with an average diameter of~15 nm.The Chol groups could synergistically insert into the surface of the bacteria via hydrophobic interaction,and the positively charged PEI could interact with the negatively charged bacteria via electrostatic interaction.It was found that NPs could effectively kill Gram-positive and Gram-negative bacteria under white light irradiation.In addition,the interaction between Chol-PEICe6 and bacteria significantly increased the production of reactive oxygen species after light illumination.More importantly,we confirmed that Chol-PEI-Ce6 had low toxicity and good biocompatibility.2.Ce6-loaded Chol-PEI for anticancer photodynamic therapyThe prepared nanomaterials have the following advantages:(1)the average size of the nanomaterials is 10-20 nm,and the passive tumor targeting is easily realized by the enhanced permeability and retention(enhanced permeation and retention effect,EPR)effect of the solid tumor;(2)the water-solubility of the photosensitizer is improved;(3)the biological toxicity is decreased.The NPs have a higher killing effect on cancer cells at low concentrations(i.e.,Ce6 concentration: 2μg/mL).In summary,the present work uses raw materials such as cationic polymer(PEI),Chol,and photosensitizer(Ce6)to prepare a new type of anticancer therapeutic agents,which can greatly improve the cell internalization and phototoxicity of the photosensitizer Ce6.We believe that such a nanoagent may have promising anticancer application.